反应详情

(3S,9aS)-3-(3-Cyano-4-fluoro-2-methylphenyl)octahydropyrazino[2,1-c][1,4]oxazin-8-ium trifluoroacetate (1.44 g, 3.70 mmol) and N-methylmorpholine (1.220 mL, 11.10 mmol) was added to DCM (25 mL). Then [6-(1H-tetrazol-1-yl)pyridin-3-yl]acetic acid (0.911 g, 4.44 mmol), HOBT (0.850 g, 5.55 mmol) and EDC (1.418 g, 7.40 mmol) were added in that order. The reaction mixture was stirred at RT for 4 h. The reaction mixture was washed with brine and saturated aq. NaHCO3 solution. The DCM layer was separated and dried over Na2SO4, filtered, and evaporated to dryness. The residue was purified by preparative TLC eluting with a 5% (10% NH4OH in Methanol): 95% chloroform solvent system to yield the title compound: 1H-NMR (500 MHz, DMSO): δ ppm 10.17 (s, 1H), 8.48 (s, 1H), 8.22 (t, J=7.35 Hz, 1H), 8.01 (s, 2H), 7.37 (s, 1H), 4.93 (s, 1H), 4.21 (dd, J=13.3, 60.75 Hz, 1H), 3.89-3.99 (m, 3H), 3.57 (dd, J=11, 23.5 Hz, 1H), 3.29 (s, 1H), 3.10-3.24 (m, 2H), 2.80-3.0 (m, 2H), 2.68 (d, J=11 Hz, 1H), 2.53 (s, 3H), 2.23-2.48 (2H).

1. washThe reaction mixture was washed with brine and saturated aq. NaHCO3 solution
2. customThe DCM layer was separated
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. customevaporated to dryness
6. customThe residue was purified by preparative TLC
7. washeluting with a 5% (10% NH4OH in Methanol)